Emma Elizabeth McGinty, MS, is a PhD Student at Johns Hopkins University Bloomberg School of Public Health, Department of Health Policy and Management. Gail L. Daumit, MD, MHS, is Associate Professor of Medicine, Psychiatry, Epidemiology, Health Policy & Management and Mental Health, Johns Hopkins Medical Institutions, Division of General Internal Medicine, Welch Center for Prevention, Epidemiology and Clinical Research.
Ms. McGinty and Dr. Daumit have disclosed no relevant financial relationships.
Address correspondence to: Gail L. Daumit, MD, MHS, 2024 E. Monument St., Room 2–513, Baltimore, MD 21205; fax: 410-614-6460; email: email@example.com.
In the overall US population, obesity is the second-leading cause of preventable death due to its role in cardiovascular disease. Obesity is one important cause of diabetes, hypertension, and high cholesterol and is also associated with some types of cancer, including colon, breast, endometrial, and gall bladder.1
Being overweight is defined as a body mass index (BMI) of 25 kg/m2; obesity is defined as a BMI of 30 kg/m2 or higher.1 In 2007–2008, 68% (95% CI, 66.3–69.8) of the US population was either overweight or obese.1 Of those, 33.8% (95% CI, 31.6–36) were obese, with a prevalence rate among men of 32.2% (95% CI, 29.5–35) and 35.5% (95% CI, 33.2–37.7) among women.1
Evidence suggests that those with serious mental illness (SMI) have higher rates of obesity than the overall US population. A 2003 study by Daumit et al, which controlled for smoking, found that 29% of men and 60% of women in a random sample of Maryland Medicaid recipients with SMI were obese compared with 18% of men and 29% of women in the National Health and Nutrition Examination Survey III (NHANES III), a nationally representative survey conducted every year by the National Center for Health Statistics.2
A 2006 review of the NHANES III database to compare rates of obesity among a group of patients with SMI receiving outpatient treatment to rates in the general population found that 41% of the men and 50% of the women with SMI were obese compared with 20% of the men and 27% of the women in the control group.3
A 1999 study used data from the National Health Interview Survey (NHIS) to compare obesity among those diagnosed with schizophrenia to those without a schizophrenia diagnosis.4 Although mean BMIs did not differ for men, women with schizophrenia had a significantly higher mean BMI than women without schizophrenia.4 For men, the mean BMI for those men with schizophrenia was 26.1 and the mean BMI for those without schizophrenia was 25.6.4 Among women, the group with schizophrenia had a mean BMI of 27.4 compared with a mean of 24.5 among those without.4 Measurement of mean BMI can hide trends in the distribution of BMI. Using the NHIS data, Allison and colleagues found that both men and women with schizophrenia were more likely to have a BMI of more than 30 when compared with those without schizophrenia.4
High rates of obesity among those with SMI likely contribute to an elevated burden of cardiovascular risk factors in this population. A 2002 study of 644 patients with bipolar disorder found that 58% of the patients were overweight, 21% were obese, and 5% were extremely obese.5 In the same study, obesity was significantly associated with hypertension.5 A 1999 study by Dixon and colleagues found that in a cohort of 719 adults with schizophrenia, 34% had been diagnosed with high blood pressure.6
A 2005 study by McEvoy and colleagues found that 47% of adult men and women with schizophrenia had high blood pressure compared with 31% of men and 27% of women without schizophrenia matched on age, race, and gender from the NHANES III study.7 McEvoy and colleagues also found that both men and women with schizophrenia had higher mean triglycerides than the general population, and that high density lipoprotein (HDL) was lower in those with schizophrenia compared with the general population.7 Elevated triglycerides and decreased HDL are strong risk factors for cardiovascular disease.
Studies show that prevalence of diabetes is at least one and a half to two times higher among those with schizophrenia than in the overall population,8,9 and that prevalence of metabolic syndrome, a group of risk factors for coronary heart disease, including abdominal obesity, dyslipidemia, increased blood pressure, insulin resistance and glucose intolerance, is also heightened among those with schizophrenia (36% among males and 52% among females) compared with the overall population (20% among males and 25% among females).7
Causes of Obesity in Serious Mental Illness
The causal pathway between SMI and obesity is not fully understood; however, the current research can be grouped into two general categories. First, there is the role of antipsychotic, antidepressant, and mood stabilizers in obesity; second, are the ways in which lifestyle factors such as diet and physical activity, poverty related to unemployment or homelessness, and institutional factors contribute to obesity. In addition, there is a high prevalence of smoking and alcohol use among this population.10
Use of Psychotropic Agents
Antipsychotic medications, some types of antidepressants, and mood stabilizers such as lithium and valproate have been shown to cause weight gain.11 All antipsychotic agents currently available in the US have been shown to increase weight gain compared with a placebo.12
In a 1999 study by Allison and colleagues, patients treated with the second-generation antipsychotic agent (SGA) clozapine gained an average of 4.5 kg during a 10-week period. Patients treated with olanzapine and risperidone gained 4.2 and 2.1 kg during the same period, respectively.13 Newcomer and Haupt reviewed data from 1975 to 2006 and concluded that the SGAs risperidone, quetiapine, amispulride, and sotepine were associated with modest increases in weight (less than 2 kg) and that olanzapine and clozapine were associated with increases of 4 to 10 kg.14 In two of the studies reviewed by Newcomer, the average weight gain was 12 kg among those patients who received the common dosages of 12.5 and 17.5 mg/day of olanzapine.15,16 Newcomer concluded that of the SGAs studied, ziprasidone and aripiprazole posed the lowest risk for weight gain.
In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study of patients with schizophrenia published in 2005, patients taking olanzapine gained more weight than patients taking other psychotropic medications. Quetiapine and risperidone were the second and third most common causes, respectively, of weight gain.17
A 2005 consensus statement issued by the American Diabetes Association, American Association of Clinical Endocrinologists, and the North American Association for the Study of Obesity concluded that clozapine and olanzapine pose the highest risk of weight gain, in addition to increased risk of diabetes and dyslipidemia.18 The organizations also concluded that quetiapine and risperidone were associated with lesser potential weight gain than clozapine and olanzapine; weight gain from aripiprazole and ziprasidone was found to be minimal.18
Some antidepressants and mood stabilizers have also been shown to cause weight gain, which in turn can lead to noncompliance. Early studies suggested that weight gain was a primary reason patients discontinued treatment on tricyclic antidepressants (TCAs) and lithium, respectively.19 Among antidepressants, TCAs in particular appear to cause weight gain.19 A literature review by Garland and colleagues found an average weight gain of 0.6 to 1.4 kg per month for the first 6 to 9 months of treatment; higher weight gain was associated more with amitriptyline than with imipramine or desipramine.20
There is little evidence on the effect of monoaminoxidase inhibitors (MAOIs) on weight gain. The evidence that does exist is mixed, with studies suggesting that phenelzine may cause weight gain,21 that tranylcypromine may suppress appetite,22 and that moclobemide has no effect on weight.23
Selective serotonin reuptake inhibitors (SSRIs) do not appear to cause weight gain, and fluoxetine even has been associated with weight loss.19 A 1997 study showed that 10% of patients taking mirtazapine gained weight, compared with 1% of patients taking a placebo, a result replicated by additional studies.24 Other antidepressants such as venlafaxine, nefazodone, and bupropion do not appear to cause weight gain.11
Among mood stabilizers, lithium definitively causes weight gain, although the amount of weight gain varies by study. A rigorous, placebo-controlled trial found that 13 of 21 patients gained 4.5 kg within a year of taking the drug compared with one of 12 patients on placebo.25
Valproate has been associated with weight gain in patients treated for epilepsy, but few studies have studied the effect on weight gain when the drug is used for treatment of mood disorders.19 A 1996 study showed weight gain in 44% to 57% of patients treated with valproate for epilepsy,26 but another study in the same year found weight gain in only 7% of those with bipolar disorder treated with the same drug.27
Data are mixed regarding weight gain patterns associated with antipsychotic medications. Some studies indicate it occurs mainly during the first year of treatment, although other studies have indicated additional weight gain over subsequent years of treatment.23 A primary mechanism for this weight gain is increased appetite due to the drugs’ effects on receptors and neurotransmitters.28 The antipsychotics olanzapine and clozapine have been shown to antagonize serotonin receptors, reducing the body’s ability to register feelings of satiety.28 These drugs have also been shown to interfere with appetite regulation through other pathways, including effects on neurotransmission of dopamine and histamine, neuropeptides, and neuroendocrine systems.19,28 TCAs have been demonstrated to affect appetite through similar pathways.19
The role of lifestyle factors in obesity among those with SMI is less well-studied than the role of medications has been. Those with SMI tend to have many of the environmental risk factors associated with cardiovascular disease such as low socioeconomic status, stigma and discrimination, and lack of social support. Poor health behaviors are also common.29
Poverty and Environmental Factors
The role of poverty in obesity among those with SMI has not been extensively studied and is therefore difficult to quantify. Adults with SMI are more likely to be unemployed, low-income, and have less than a high school education than adults without SMI. Those with SMI also have high rates of homelessness, incarceration, and hospitalization, factors that may interrupt health behaviors and medication regimens to prevent and control cardiovascular disease risk factors.30 For example, in the pilot of the Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation (ACHIEVE), investigators found that food choices offered in two psychiatric rehabilitation programs in Maryland did not meet nutritional guidelines.31 It is also possible that those with SMI live in neighborhoods with less access to healthy foods, or have difficulty affording healthy foods.
Evidence suggests that those with SMI consume high-fat diets with few fruits and vegetables. A 2003 Scottish survey of 102 patients with schizophrenia showed that 33% of men with schizophrenia ate fresh fruit once or more per day32 compared with 46% of males in the overall Scottish population. Twenty-five percent of men with schizophrenia ate raw vegetables or salad twice or more per week compared with 45% of men in the overall population who ate similar amounts.32
Males with schizophrenia also consumed fewer vegetables than males in the overall population (10% vs. 39% for green vegetables five times per week).32 In addition, 50% of men with schizophrenia used skim or semi-skim milk compared with 63% of men in the overall population.32 Among women, significantly fewer with schizophrenia ate raw vegetables or salad twice per week or more compared with those in the overall population (40% vs. 59%). Women with schizophrenia were also less likely to use skim or semi-skim milk than women in the general population (50% vs. 69%).32
A 2003 study by Strassnig and colleagues compared dietary patterns in 146 patients with schizophrenia in an outpatient setting to the general population and found no significant differences in percentage of calories derived from fat, protein, and carbohydrates between the two groups.33 However, patients with schizophrenia ate significantly more calories than the general population, suggesting that those with SMI may consume more calories than those without SMI, even when composition of the foods eaten are similar.33
Physical Activity Levels
The few published studies describing physical activity levels among those with SMI report levels as low as or lower than the general population.32,34 A 1999 study by Brown and colleagues interviewed 135 patients with schizophrenia and found they had less leisure physical activity than members of the overall population of England.34 The same study found that most patients with schizophrenia were unemployed and therefore had less work-related physical activity than the overall population.34
In a 2005 study, Daumit and colleagues compared physical activity in a community-based sample of those with SMI to the US overall population and found that 26% of those with SMI had no leisure time physical activity in the past month compared with 17% in the general population.35 A 2009 study by Jerome and colleagues showed that only 4% of overweight and obese adults with SMI achieved the public health recommendation of 150 minutes or more of moderate or vigorous physical activity per week.36
Consequences of Obesity in Serious Mental Illness
Quality of Life
Obesity not only contributes to cardiovascular risk factors, but also is negatively related to quality of life among those with SMI. In a 2003 study by Allison and colleagues of 286 patients with schizophrenia taking antipsychotic medications, researchers found that 56% of participants gained weight during a 6-month period; 14% gained more than 20 lb; and weight gain was related to poorer quality of life and reduced well-being and vitality.37
A 2003 study by Strassnig and colleagues assessed the association between body weight and quality of life among patients with schizophrenia receiving outpatient care. Those with schizophrenia who were obese had worse physical functioning, worse general health, and more difficulty fulfilling the duties of daily roles such as parent, spouse, or employee than those with schizophrenia who were not obese.38
In 2008, Kolotkin and colleagues studied obesity and quality of life among 211 people participating in psychiatric outpatient, day treatment, case management, and rehabilitation programs. Data showed that 63% of those with schizophrenia and 68% of those with bipolar disorder were obese. People who were obese reported worse overall and weight-related quality of life.39
Patients with SMI have higher rates of obesity and cardiovascular risk factors related to obesity, including hypertension, high cholesterol, and diabetes, than the overall population. Factors likely to contribute to obesity among this population include: psychotropic medications that increase appetite; lifestyle factors; poverty; and environment. Furthermore, obesity decreases quality of life among those with SMI.
- Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999–2008. JAMA. 2010;303(3):235–241. doi:10.1001/jama.2009.2014 [CrossRef]
- Daumit GL, Clark JM, Steinwachs DM, Graham CM, Lehman A, Ford DE. Prevalence and correlates of obesity in a community sample of individuals with severe and persistent mental illness. J Nerv Ment Dis. 2003;191(12):799–805. doi:10.1097/01.nmd.0000100923.20188.2d [CrossRef]
- Dickerson FB, Brown CH, Kreyenbuhl JA, and colleagues. Obesity among individuals with serious mental illness. Acta Psychiatr Scand. 2006;113(4):306–313. doi:10.1111/j.1600-0447.2005.00637.x [CrossRef]
- Allison DB, Fontaine KR, Heo M, et al. The distribution of body mass index among individuals with and without schizophrenia. J Clin Psychiatry. 1999;60(4):215–220. doi:10.4088/JCP.v60n0402 [CrossRef]
- McElroy SL. Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry. 2002;63:207–213. doi:10.4088/JCP.v63n0306 [CrossRef]
- Dixon L, Postrado L, Delahanty J, Fischer PJ, Lehman A. The association of medical comorbidity in schizophrenia with poor physical and mental health. J Nerv Ment Dis. 1999;187(8):496–502. doi:10.1097/00005053-199908000-00006 [CrossRef]
- McEvoy JP, Meyer JM, Goff DC, et al. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005;80(1):19–32. doi:10.1016/j.schres.2005.07.014 [CrossRef]
- Dixon L, Weiden P, Delahanty J, and colleagues. Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull. 2000;26(4):903–912.
- Bresee LC, Majumdar SR, Patten SB, Johnson JA. Prevalence of cardiovascular risk factors and disease in people with schizophrenia: a population-based study. Schizophr Res. 2010;117(1):75–82. doi:10.1016/j.schres.2009.12.016 [CrossRef]
- Dickerson FB, Brown CH, Daumit GL, et al. Health status of individuals with serious mental illness. Schizophr Bull. 2006;32(3):584–589. doi:10.1093/schbul/sbj048 [CrossRef]
- Fava M. Weight gain and antidepressants. J Clin Psychiatry. 2000;61(11S):37–41.
- Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19Suppl 1:1–93. doi:10.2165/00023210-200519001-00001 [CrossRef]
- Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156(11):1686–1696.
- Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Can J Psychiatry. 2006;51(8):480–491.
- Nemeroff CB. Dosing the antipsychotic medication olanzapine. J Clin Psychiatry. 1997;58(10S):45–49.
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- Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353(12):1209–1223. doi:10.1056/NEJMoa051688 [CrossRef]
- American Diabetes Association. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004;27:596–601.
- Zimmermann U, Kraus T, Himmerich H, Schuld A, Pollmächer T. Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients. J Psychiatr Res. 2003;37(3):193–220. doi:10.1016/S0022-3956(03)00018-9 [CrossRef]
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- Balon R, Yeragani VK, Pohl R, Merlos B, Sherwood P. Changes in appetite and weight during the pharmacological treatment of patients with panic disorder. Can J Psychiatry. 1993;38(1):19–22.
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- Silverstone T. Moclobemide vs imipramine in bipolar depression: a multicentre double-blind clinical trial. Acta Psychiatr Scand. 2001;104:104–109. doi:10.1034/j.1600-0447.2001.00240.x [CrossRef]
- Davis R, Wilde MI. Mirtazapine. A review of its pharmacology and therapeutic potential in the management of major depression. CNS Drugs. 1996;5:389–402. doi:10.2165/00023210-199605050-00007 [CrossRef]
- Peselow ED, Dunner DL, Fieve RR, Lautin A. Lithium carbonate and weight gain. J Affect Disord. 1980;2(4):303–310. doi:10.1016/0165-0327(80)90031-2 [CrossRef]
- Isojärvi JI, Laatikainen TJ, Knip M, Pakarinen AJ, Juntunen KT, Myllylä VV. Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol. 1996;39(5):579–584. doi:10.1002/ana.410390506 [CrossRef]
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- Draine J, Salzer MS, Culhane DP, Hadley TR. Role of social disadvantage in crime, joblessness, and homelessness among persons with serious mental illness. Psychiatr Serv. 2002;53(5):565–573. doi:10.1176/appi.ps.53.5.565 [CrossRef]
- Casagrande SS, Jerome GJ, Dalcin AT, et al. Randomized trial of achieving healthy lifestyles in psychiatric rehabilitation: the ACHIEVE trial. BMC Psychiatry. 2010;10:108. doi:10.1186/1471-244X-10-108 [CrossRef]
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- Strassnig M, Brar JS, Ganguli R. Nutritional assessment of patients with schizophrenia: a preliminary study. Schizophr Bull. 2003;29(2):393–397.
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